Numerous projects are using Doxygen, and I think you won't go wrong to pick that one as your choice. I've previously been involved in a portion of a much larger project that used Doxygen during their build process, do I didn't get into the actual doc generation part of the build, but adding the comments was easy and straight forward .
If your project is large with sub-systems written in different languages, then Doxygen is beneficial because of the many languages it supports: C++, C, Java, Objective-C, Python, IDL (Corba and Microsoft flavors), Fortran, VHDL, PHP, C#, and to some extent D.